Carboxyhc acid protonated

Initially, a loosely bound hydrogen bonded adduct 10 is formed, from the carboxyhc acid 8 and the carbonyl compound 6. The next step is the formation of the a-adduct 11 by reaction of the isocyanide with the nucleophilic carboxylate and the electrophilic protonated carbonyl compound. a-Adduct 11 then rearranges to give oc-acyloxy amide 9. 

The final example is the most complicated one. There is a normal OH group pK about 16) and a slightly acidic ahcyne (pJbasic group is not a normal amine but an amidine in which the two nitrogen atoms can combine (see arrows) to capture a proton. It will have a pKa of about 12 and so would even be protonated by a phenol though most chemists would use a carboxyhc acid. 

FIGURE 5.64 The 300-MHz spectrum of the diastereotopic methylene hydrogens in citric acid. While there is no adjacent stereocenter, restricted rotation renders these hydrogens nonequivalent. The resonances of the protons of the carboxyhc acid and hydroxyl groups are not shown. 

Carboxylic acids are weak organic acids that exhibit the following characteristics of acids (1) nndergo dissociation in aqueous solutions, forming a carboxylate ion RCOO and H+ (proton) or a hydronium ion, H3O+ (hydronium) (2) transfer protons to bases forming salts and (3) the water-soluble acids have a sour taste. The carboxyhc acids are characterized by carboxyl functional groups. 

The proton-active modifiers which were used for controlled protonolysis of the active Al—C bonds include long chain alcohols, carboxyhc acids, silanols, proton-active surfactants, and sugars (see Table 2.4). 

In the second compound there are three possibilities. The acidic proton of the carboxyhc acid and the electrophihc C=0 bond are both possible reaction sites, but now so is the positively charged phosphorus. Phosphorus comes below nitrogen in the periodic table so, unlike N, it can have five bonds. 

In acid solution the first reaction is similar, though the tetrahedral intermediate is neutral, and the carboxyl is still the better leaving group. The second esterification is now all right because methanol can attack the protonated carboxyhc acid and water can be driven out after a second protonation. The second step is an equihbrium, with water and methanol about equal as leaving groups, but methanol is present in large excess as the solvent and drives the equihbrium across. We have omitted proton transfer steps. 

Direct derivatives of carboxyhc acids are different functional groups which maintain an acidic proton and a hydrogen bond acceptor (the carbonyl) in order to have similar specific interactions with the receptor. Among the most common direct derivatives can be listed the hydroxamic acids (R—CO— NH—OH), the acylcyanamides (R—CO— NH—CN) and the acylsulfonamides (R—CO—NH- 02—R ) (Table 15.11). 

Amino acids, peptides, and proteins typically contain both acidic and basic functional groups such as carboxyl and amino groups. CarboxyHc acids with a pK of 5 can easily protonate an amine (pKj, 4) in aqueous solution, and therefore molecules containing both carboxyl and amino groups are found to be zwitterions... 

When a base is added to a solution of the net cationic form of alanine (initially at pH 0, for example), the first proton removed is the carboxyhc add proton, as we have said. In the case of alanine, when a pH of 2.3 is reached, the carboxylic acid proton will have been removed from half of the molecules. This pH represents the pA of the alanine carboxylic acid proton, as can be demonstrated using the Henderson— Hasselbalch equation. 

Throughout the chapter it is important to keep in mind that carboxylic acids are, clearly, acidic. Generally, carboxyhc acids are weak acids in that proton donation to water is incomplete and thus carboxylic acids are not completely ionized. So, as pointed out earlier (Chapter 5), the add strength or addity is referred to as the position of equilibrium in the reaction of the acid with a base. Thus, for the generalized acid RCO2H ionizing in water (H2O), Equation 9.75 can be written ... 

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